1. Imatinib Resistance and Progression of CML to Blast Crisis: Somatic Hypermutation AIDing the Way 
Matthew P. Strout, David G. Schatz 
Cancer Cell 
Volume 16, Issue 3, Pages (September 2009)
DOI: /j.ccr
Copyright © 2009 Elsevier Inc. Terms and Conditions

2. Figure 1
Model of CML Evolution, Lineage Conversion, and Acquisition of Imatinib-Resistant BCL-ABL1 Mutations
In chronic-phase CML, differentiation of a Ph+ HSC along the myeloid lineage predominates, with >95% of circulating Ph+ cells being mature granulocytes. The remaining cells differentiate along the B lymphoid lineage, giving rise to a small population of mature Ph+ B cells. However, in Ph+ B lymphoid progenitors, expression of PAX5 can lead to upregulation of AID with aberrant somatic hypermutation of BCR-ABL1 and acquisition of imatinib resistance. Lineage conversion from B lymphoid progenitor to myeloid progenitor (or differentiation of a PAX5 and AID-expressing CML HSC along the myeloid lineage) would allow AID-generated mutations to appear in myeloid cells. Blast crisis subsequently evolves from a Ph+ B lymphoid, mixed-lineage, or myeloid progenitor that contains additional genetic alterations.
Cancer Cell  , DOI: ( /j.ccr )
Copyright © 2009 Elsevier Inc. Terms and Conditions